Roche has reported wins for its BTK inhibitor fenebrutinib in a pair of phase 3 studies across two multiple sclerosis (MS) populations. One victory was based on the finding that the candidate was noninferior to Ocrevus, despite the company originally designing (PDF) the study to show superiority to the incumbent MS treatment.
The other study, dubbed Fenhance, is one of two pivotal trials Roche is conducting in relapsing MS patients. This study linked fenebrutinib to a significant drop in annualized relapse rate compared to Sanofi's Aubagio over at least 96 weeks of treatment. The reduction in relapses compared to Aubagio met the trial’s primary endpoint, according to this morning's release from Roche's Genentech unit.
Roche also reported a hit on the primary endpoint of Fentrepid, a trial that compared fenebrutinib to the Swiss drugmaker’s own anti-CD20 antibody Ocrevus in patients with primary progressive MS (PPMS). The company said fenebrutinib was noninferior to Ocrevus, the only approved PPMS drug, as measured by a delay in the onset of composite confirmed disability progression over at least 120 weeks of therapy.
Fenebrutinib performed better numerically than Ocrevus starting in Week 24, Roche said, and that edge lasted throughout the observation period. However, the company only claimed statistical noninferiority, not superiority.
Roche and its physician collaborators called Fentrepid a superiority study versus ocrelizumab, the generic name for Ocrevus, in a presentation in 2020. The ClinicalTrials.gov listing for Fentrepid makes no mention of whether the trial is designed to show superiority or noninferiority.
Morgan Stanley analyst Sarita Kapila, M.D., asked Roche at an investor event in September to confirm whether it had changed the endpoint to noninferiority and, if so, whether it could make such a change “so close to the trial ending.” Levi Garraway, M.D., Ph.D., head of global product development at Roche, told Kapila “we cannot comment right now on discussions around what we might or might not do in PPMS.”
Roche reported the primary endpoint wins alongside a high-level look at safety. Liver safety, a concern with BTK inhibitors, was consistent with previous fenebrutinib studies, the company said. Roche is still evaluating additional safety data and plans to share full results at upcoming medical meetings.
The company will consider the data for submission to regulators once it has results from the second Fenhance study. Data from that trial, which has a similar design to today's Fenhance study, are due in the first half of next year.
Roche is one of a clutch of drugmakers that have targeted BTK. Sanofi’s tolebrutinib is under FDA review, although the agency recently delayed a decision by three months and two trials in relapsing MS missed their primary endpoints. Sanofi, which, like many of its rivals, has reported liver safety signals, is seeking approval in non-relapsing secondary progressive MS.
Meanwhile, Merck KGaA axed its BTK inhibitor evobrutinib after failing to beat Aubagio in two relapsing MS studies. Biogen exited the BTK race in 2023, but Zenas BioPharma recently paid $100 million for rights to that drug. Novartis has its own candidate in phase 3 development in relapsing and secondary progressive MS.